Computational studies confirmedthe gorge-wide occupancy of both enzymes, from the main site to asecondary site, including a so far non-described AChE cryptic pocket.The lead compound displayed in vitro dual nanomolar potencies, adequatebrain permeability, aqueous solubility, human microsomal stability,lack of neurotoxicity, and it rescued memory, synaptic plasticity,and neuroinflammation in an AD mouse model, after low dose chronicoral administration. Here, ACHE is linked to Alzheimer disease.